Embryonic Stem Cells Develop into Functional Dopaminergic Neurons after Transplantation in a Parkinson Rat Model

Although implantation of fetal dopamine (DA) neurons can reduce parkinsonism in patients, current methods are rudimentary, and a reliable donor cell source is lacking. We show that transplanting low doses of undifferentiated mouse embryonic stem (ES) cells into the rat striatum results in a prolifer...

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Published in:	Proceedings of the National Academy of Sciences - PNAS Vol. 99; no. 4; pp. 2344 - 2349
Main Authors:	Björklund, Lars M., Sánchez-Pernaute, Rosario, Chung, Sangmi, Andersson, Therese, Iris Yin Ching Chen, Kevin St. P. Mc Naught, Brownell, Anna-Liisa, Jenkins, Bruce G., Wahlestedt, Claes, Kim, Kwang-Soo, Isacson, Ole
Format:	Journal Article
Language:	English
Published:	United States National Academy of Sciences 19-02-2002 National Acad Sciences The National Academy of Sciences
Series:	From the Cover
Subjects:	Adrenergic Agents - pharmacology Amphetamine - pharmacology Animals Biological Sciences Biology Brain Cell Culture Techniques - methods Cell lines Cell Transplantation Cellular differentiation Dopamine - metabolism Dopamine Agents - pharmacology Embryo, Mammalian - cytology Embryonic stem cells Immunohistochemistry Ligands Medicin och hälsovetenskap Neural stem cells Neurology Neurons Neurons - cytology Neurons - metabolism Neurons - transplantation Neuroscience Oxidopamine - pharmacology Parkinson Disease - therapy Parkinson's disease Rats Rodents Rotation Stem cells Stem Cells - metabolism Time Factors Tissue grafting Tomography, Emission-Computed Transplantation
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Summary:	Although implantation of fetal dopamine (DA) neurons can reduce parkinsonism in patients, current methods are rudimentary, and a reliable donor cell source is lacking. We show that transplanting low doses of undifferentiated mouse embryonic stem (ES) cells into the rat striatum results in a proliferation of ES cells into fully differentiated DA neurons. ES cell-derived DA neurons caused gradual and sustained behavioral restoration of DA-mediated motor asymmetry. Behavioral recovery paralleled in vivo positron emission tomography and functional magnetic resonance imaging data demonstrating DA-mediated hemodynamic changes in the striatum and associated brain circuitry. These results demonstrate that transplanted ES cells can develop spontaneously into DA neurons. Such DA neurons can restore cerebral function and behavior in an animal model of Parkinson's disease.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 Edited by Gerald D. Fischbach, Columbia University College of Physicians and Surgeons, New York, NY, and approved November 29, 2001 To whom reprint requests may be addressed. E-mail: isacson@helix.mgh.harvard.edu or lars.bjorklund@mclean.harvard.edu.
ISSN:	0027-8424 1091-6490
DOI:	10.1073/pnas.022438099